Anti-phosphoenolpyruvate carboxykinase 2 antibody in patients with autoimmune hepatitis

Hepatol Res. 2014 Sep;44(9):1019-25. doi: 10.1111/hepr.12276. Epub 2014 Jan 27.

Abstract

Aim: To identify a novel autoantibody specific to autoimmune hepatitis (AIH) and to evaluate its clinical significance.

Methods: Non-nuclear component protein extracted from normal human liver cell CyrohNHpes cultures that reacted with sera from AIH patients on a western blot was identified as an antigenic protein and subjected to N-terminal amino acid analysis to identify phosphoenolpyruvate carboxykinase 2 (PCK2). Enzyme-linked immunoassay (ELISA) for anti-PCK2 antibody was conducted on sera samples from patients with AIH (n = 42), primary biliary cirrhosis (PBC; n = 48), non-alcoholic steatohepatitis (NASH, n = 41), chronic hepatitis C (CHC, n = 20), drug-induced liver injury (DILI, n = 10), systemic lupus erythematosus (SLE, n = 16) and on sera samples from healthy volunteers (n = 30). Clinical findings were compared for AIH patients testing positive and negative for anti-PCK2 antibody.

Results: ELISA findings showed that mean anti-PCK2 antibody titer in sera from AIH patients was significantly higher than in PBC, NASH, CHC, DILI and SLE patients, as well as in healthy volunteers. Anti-PCK2 antibody was present in 50.0% (21/42) of AIH, 14.6% (7/48) of PBC, 4.9% (2/41) of NASH, and 10.0% (2/20) of CHC patients, 0% (0/10) of DILI, 12.5% (2/16) of SLE and in 3.3% (1/30) of healthy volunteers. The sensitivity, specificity and accuracy of using the detection of anti-PCK2 antibody in diagnosing AIH were 50.0%, 91.5% and 83.1%, respectively. None of the AIH patients positive for anti-PCK2 antibody showed characteristic clinical features.

Conclusion: Although further investigations into the clinical usefulness are necessary, anti-PCK2 may have potential as a diagnostic marker for AIH.

Keywords: autoantibody; autoimmune hepatitis; non-alcoholic steatohepatitis; phosphoenolpyruvate carboxykinase 2; primary biliary cirrhosis.